AUTHOR INFORMATION

Section 1 of 12

Authored by Eric S Chin, MD, Consulting Staff, Department of Emergency Medicine, Kaiser Permanente Hospital, S San Francisco

Eric S Chin, MD, is a member of the following medical societies: American College of Emergency Physicians

Edited by Debra Slapper, MD, Consulting Staff, Department of Emergency Medicine, St Anthony's Hospital; Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc; Grace M Young, MD, Associate Professor, Department of Pediatrics, University of Maryland Medical Center; John Halamka, MD, Chief Information Officer, CareGroup Healthcare System, Assistant Professor of Medicine, Department of Emergency Medicine, Beth Israel Deaconess Medical Center; Assistant Professor of Medicine, Harvard Medical School; and Richard G Bachur, MD, Assistant Professor of Pediatrics, Harvard Medical School; Associate Chief and Fellowship Director, Division of Emergency Medicine, Children's Hospital of Boston

Author's Email:	Eric S Chin, MD
Editor's Email:	Debra Slapper, MD

eMedicine Journal, November 8 2006, VOLUME 7, Number 11

INTRODUCTION

Section 2 of 12

Background: Not all children who wheeze have asthma. Most children younger than 3 years who wheeze are not predisposed to asthma. Only 30% of infants who wheeze go on to develop asthma. Reactive airway disease has a large differential diagnosis and must not be confused with asthma.

Clinical factors suggestive of childhood asthma include recurrent wheezing, symptomatic improvement with a bronchodilator, recurrent cough, exclusion of alternative diagnoses, and suggestive peak flow findings.

Pathophysiology: Numerous environmental stimuli induce an allergen-antibody interaction, causing a release of mediators that create airway inflammation. Airway inflammation is the primary factor responsible for smooth muscle hyperresponsiveness, edema, and increased mucous production, resulting in increased work of breathing. A complex interaction occurs between inflammatory cells and airway epithelium. Mediators released from mast cells induce edema, mucous secretion, and bronchospasm. These mediators include histamine, tryptase, heparin, leukotrienes, platelet-activating factor, cytokines, interleukins, and tumor necrosis factor. The other inflammatory cells (ie, eosinophils, lymphocytes) also release mediators and create a toxic environment to respiratory epithelial cells.

In infants and children younger than 3 years, the intrapulmonary airways are so small that any lower airway infection results in diminished airway function. Other anatomical factors, such as poor collateral ventilation, decreased elastic recoil pressure, and a partially developed diaphragm, may predispose the very young child to respiratory compromise.

Speculation exists that all infants are born with highly responsive airways. Increased immunoglobulin E (IgE) levels have been found in those younger than 2 years. A decrease in airway responsiveness may be associated with environmental allergens, viral respiratory diseases, and hereditary factors.

Breastfeeding might protect children younger than 24 months of age against recurrent wheezing. The cytokine, TGF-B1, in human milk may have both suppression and enhancement functions in the immune reaction.

Exposure to maternal environmental tobacco smoke during pregnancy or the first year appears to predispose children to reactive airway disease.

Current research on the genetic basis for the pathogenesis of asthma may lead to new diagnostic and preventive treatments. The ADAM33 gene on the short arm of chromosome 20 is hypothesized as being important in the development and pathogenesis of asthma.

Frequency:

• In the US: Risk of developing asthma is 7% if neither parent has asthma, 20% if one parent has asthma, and 64% if both parents have asthma. In the United States, approximately one half of all ED and clinic visits for asthma are children younger than 18 years. Pediatric asthma is a chronic, multifactorial, lower airway disease that affects 5-15% of children (2.7 million children in the United States alone). ED visits peak in the fall. School holidays disrupt the spread of infections with a subsequent decrease in hospitalization. Asthma prevalence appears to be increasing worldwide. Air pollutants may play a role in the prevalence increase. Higher prevalence occurs in poverty stricken urban areas where children are less likely to have routine doctor visits and access to the availability of medications.

  A correlation may exist between high levels of exposure to cockroach allergen and the frequency of asthma-related health problems in inner-city children. Homes in poverty areas were more likely to have high cockroach allergen levels. Asthma may develop in children from early exposure to cockroach allergen.

  Status asthmaticus appears to be on the rise; several retrospective studies reflect an increase in hospital admissions, particularly in those younger than 4 years. Fewer hospital and ED visits are needed in children using inhaled corticosteroid therapy.

• Internationally: Worldwide, the prevalence of asthma is increasing. Asthma is found to be more common in Western countries than in developing countries. Asthma is more prevalent in English-speaking countries. Prevalence increases as a developing country becomes more Westernized and urbanized.

Mortality/Morbidity:

• One third of all children younger than 18 years are significantly affected.

• Reactive airway disease accounts for 13 million physician visits annually in the United States and 200,000 hospitalizations for which approximately $1.8 billion is spent annually.

• Mortality rates are increasing despite new pharmacologist advances.

Race: Reactive airway disease is more common in black and Hispanic children; hospitalization rates in African Americans are 4 times greater than in the white population.

No correlation exists with income or education level from a retrospective review.

Sex: The male-to-female ratio is 1.5:1

Age: The peak prevalence of asthma is in those aged 6-11 years.

CLINICAL

Section 3 of 12

History:

• The following information should be elicited:
  • Initiation of symptoms (More than a few days decreases the chance of quick reversal in the ED because of prolonged inflammation and mucous plug formation.)

• Upper respiratory infection (URI) symptoms, fever, and production of phlegm

• Precipitating factors

• Use of an bronchodilator inhaler; how often it was used in the past 24-48 hours prior to the ED visit; how often it was used over the past week or month

• Compliance with use of corticosteroid inhaler (Ask if it was used daily despite any symptoms of wheezing.)

• Date of last ED visit; how severe the current episode is compared with previous episodes

• Date of the last hospital admission

• Number of admissions in the past year; number of intensive care unit admissions

• History of intubation and how long ago it was

• Recent use of oral steroids

• Factors that usually initiate symptoms

• Whether this is a typical episode

• Presence of any underlying cardiac, GI, or immunologic diseases

• Other current medications

• Exposure to tobacco smoke and allergens (ie, cat dander)

• Ability to tolerate fluids

• Recent mental status changes

• Baseline peak expiratory flow rate (PEFR)

• History of atopic dermatitis or other allergic skin conditions

• Dry cough that is often worse at night

• History of recurrent wheezing and dyspnea

• Wheeze or cough after active playing

• Relationship to emotional expressions

• Relationship to menses

Physical:

• Fever

• Tachycardia

• Tachypnea, dyspnea

• Wheezing

• Coughing

• Flushing, cyanosis

• Flaring of nasal alae

• Presence of nasal polyps and nasal secretions

• Intercostal retractions

• Poor feeding

• Diaphoresis

• Distant breath sounds, hyperresonance (Beware of "silent chest," too little air movement to hear wheezing.)

• Pulsus paradoxus (mild asthma pulsus paradoxus = 10, moderate = 10-20, severe >20)

• Altered mental status

• Decreased peak expiratory flow rate

• Inspiratory-to-expiratory ratio (An increased inspiratory-to-expiratory ratio is a bad sign.)

• Allergic shiner (ie, dark semicircles of skin under the eyes)

• Transverse nasal skin fold from repeatedly rubbing the nose

• Increased anteroposterior diameter or pectus carinatum

• Murmur

• Clubbing

• Subcutaneous emphysema

Causes:

• Precipitants of asthma exacerbation

• Infection - Respiratory syncytial virus (RSV) most commonly isolated from infants and preschool-aged children; Mycoplasma pneumoniae most commonly isolated from school-aged children

• Tobacco smoke

• Pet dander, cockroach and dust mite allergen

• Molds

• Pollen

• Exercise

• Weather changes

• Stress

• Drugs

• A precipitant of bronchiolitis is respiratory infection, usually due to RSV.

• Gastroesophageal fistula

• Mediastinal mass (external compression of the airway)

• Cystic fibrosis

DIFFERENTIALS

Section 4 of 12

Anaphylaxis
Pediatrics, Anaphylaxis
Pediatrics, Croup or Laryngotracheobronchitis
Pediatrics, Foreign Body Ingestion
Pediatrics, Pneumonia
Pediatrics, Respiratory Distress Syndrome
Pneumonia, Aspiration

Other Problems to be Considered:

Cystic fibrosis
Enlarged mediastinal mass
Gastroesophageal reflux (GER)
Laryngeal webs
Roundworms
Tracheoesophageal fistula
Vascular rings
Ventricular septal defect (VSD)

WORKUP

Section 5 of 12

Lab Studies:

• A complete blood count (CBC) may be indicated for a suspected viral infection (lymphocytosis, leukopenia), parasitic infection (eosinophilia), or hemosiderosis.

• An arterial blood gas (ABG) determination should be performed for any patient in status asthmaticus to check for hypoxia, hypercarbia, or acidosis.

• An assessment of electrolyte levels may reveal hypokalemia in patients who are using albuterol long-term.

• Although theophylline is prescribed less frequently, a theophylline level is useful for those on the drug.

Imaging Studies:

• Chest radiography

• Hyperinflation

• Peribronchial thickening

• Atelectasis

• Radiographs may provide evidence of foreign body, associated vascular anomalies, cardiac enlargement, pulmonary hypertension, infiltrates, or masses.

• Some recommend discriminate use of chest radiography to look for focal infiltrate in patients who are wheezing for the first time. Indications include history of fever (temperature >100.4°F), an absence of a family history of asthma, or localized wheeze or rales on examination.

Other Tests:

• All chronically wheezing infants and children with chronic asthma should have a sweat chloride test for cystic fibrosis at a subsequent primary care provider (PCP) visit or during inpatient evaluation.

• A tuberculosis skin test may be indicated if significant risk factors exist.

• Allergy testing

• Exercise tolerance testing

Procedures:

• Spirometry (decreased forced expiratory volume in one second [FEV₁])

• Bedside spirometry is the primary procedure for children with RAD who are older than 5 years.

• Patients with decreased FEV₁ require further evaluation and treatment.

• A barium swallow may be indicated to determine any esophageal, pulmonary, or vascular pathology, particularly a tracheoesophageal fistula.

• Bronchoscopy (rarely indicated)

  Table 1. Peak Flow Rates in Liters per Minute
  
  
  

  Height in Inches	Average Rate	Range*	Height in Inches	Average Rate	Range*
  40	150	110-190	56	330	240-420
  41	160	115-205	57	340	240-420
  42	170	120-220	58	360	260-460
  43	180	130-220	59	375	270-480
  44	190	135-245	60	390	280-500
  45	200	145-255	61	400	290-510
  46	210	150-270	62	415	300-530
  47	220	160-280	63	430	310-550
  48	230	165-295	64	445	320-570
  49	240	175-305	65	460	330-590
  50	250	180-320	66	480	345-615
  51	260	190-330	67	500	360-640
  52	270	195-345	68	515	370-660
  53	280	200-360	69	530	380-680
  54	300	215-385	70	550	395-705
  55	315	225-405	71	570	410-730

  
  

  * Includes 95% of white males aged 7-20 years.

  Derived and adapted from J Pediatr 1979;95:192-6.

• Peak expiratory flow (PEF) is the most common form of pulmonary function test monitoring. Record the best of 3 attempts. Possible life-threatening asthma exacerbation with PEF predicted of less than 30%; severe exacerbation, with less than 50%; and moderate exacerbation, with less than 80%.

TREATMENT

Section 6 of 12

Prehospital Care: Provide oxygen during transport, cardiorespiratory monitoring and pulse oximetry, beta-agonist nebulization, and intravenous access if the patient is in moderate-to-severe respiratory distress. Subcutaneous terbutaline or epinephrine may be considered if severe distress and very poor air movement are present.

Emergency Department Care: The initial components for ED management of reactive airway disease are oxygen, FEV₁ or PEF by spirometry, and hydration with isotonic fluids.

Optimal management of status asthmaticus includes continuous inhaled beta-agonist of 0.5 mg/kg/h, inhaled ipratropium, intravenous corticosteroid (2 mg/kg/dose), and intravenous magnesium of 40 mg/kg given concurrently for the child in moderate-to-severe respiratory distress.

Frequent evaluation of the patient's cardiorespiratory status is imperative. If a child fails to improve with these interventions, admission to an ED observation area, inpatient unit, or pediatric critical care unit should be initiated. Continued failure to respond with mental status changes is an ominous finding and suggests rising pCO₂. Consider noninvasive positive pressure ventilation (PPV) (eg, continuous positive airway pressure [CPAP] 3-5 cm H₂O, intermittent positive airway pressure [IPAP] 10-18 cm H₂O) prior to rapid sequence intubation. Consider the increased risk of pneumothorax if intubated. Optimize ventilator settings.

• Avoid intubation if possible.
  • Consider all other measures first (eg, bilevel positive airway pressure, continuous beta-agonist, helium-oxygen mixture [heliox]).

  • Consider ketamine for sedation/dissociative state, 1 mg/kg IV (provides 15 min anesthesia and may provide further bronchodilation for up to 30 min).

  • For rapid sequence intubation, succinylcholine, 2 mg/kg IV preceded by atropine 0.02 mg/kg in the pediatric patient (older adolescent: 1-1.5 mg/kg IV without atropine) may be used.

  • Tube size = (age/4) + 4

  • Avoid nasal intubation. Oral intubation allows for a larger tube size and easier access for suctioning and bronchoscopy.

• Albuterol

• Aerosolized albuterol, a beta2-agonist, relieves bronchospasm.

• Although studies suggest that delivery of albuterol by metered dose inhaler (MDI) with spacer is equally as effective as nebulization in children as young as 2 years, nebulization is recommended for those younger than 6 years or those with severe asthma or poor air movement. Infants and small children need doses of MDI equivalent to those used by adults because of decreased retention time of the drug in the lung, because of their inability to hold their breath, and because the size of the airway limits delivery of medication.

• The use of chlorofluorocarbon (CFC) inhalers is being phased out to protect the ozone layer. A decreased ozone layer may lead to health and environmental problems. No difference exists in efficacy between CFC and non-CFC inhalers.

• Continuous albuterol nebulization may reduce the need for endotracheal intubation in status asthmaticus.

• Levalbuterol, the single isomer, may result in higher patient discharge rates from the ED or hospital and hence may be more cost-effective than the traditional, racemic albuterol given.

• Ipratropium: The combination of a beta-adrenergic agonist and ipratropium improves FEV₁ more effectively than either agent used alone. Other anticholinergics, such as glycopyrrolate, also may be nebulized.

• Corticosteroids

• Prednisone or prednisolone given early during ED treatment reduces hospital admission rates. The dosages for both are 2 mg/kg/dose. Prednisone, in tablet form, is given to older children or adolescents. Prednisolone can be given orally (Prelone), or parenterally (Solu-Medrol). Prednisolone is preferred for the younger child or for those who cannot tolerate oral administration (eg, vomiting, severe respiratory distress, altered mental status).

• Nebulized corticosteroids could prove useful in the ED setting. Further studies are pending.

• Oral beta2-agonists have no role in the acute setting. Oral beta-agonists may be beneficial in preschool children for outpatient therapy.

• Theophylline has no role in the acute setting. It may be considered for outpatient treatment in patients with poor compliance with inhaled beta-agonist and for patients with nocturnal asthma exacerbation.

• Magnesium at 40 mg/kg IV may provide a "therapeutic bridge." Studies remain in conflict regarding magnesium's effectiveness.

Consultations:

• Pediatric emergency medicine specialist

• Pediatric critical care specialist

• Pediatric pulmonary specialist

MEDICATION

Section 7 of 12

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Drug Category: Beta-adrenergic agonists -- These agents relieve reversible bronchospasm by relaxing smooth muscles of the bronchi. Systemic beta-agonists allow systemic delivery of medication to the pulmonary system in medical conditions where bronchoconstriction may inhibit delivery of medication to desired site because of little to no air movement. Less effective than inhaled beta-adrenergic agonists. Use is falling into disfavor. Does not appear to alter admission.

Drug Name	Albuterol (Ventolin, Proventil) -- Beta-agonist for bronchospasm refractory to epinephrine. Relaxes bronchial smooth muscle by action on beta2-receptors with little effect on cardiac muscle contractility. May decrease mediator release from mast cells and basophils and inhibit airway microvascular leakage. Continuous therapy may reduce need for mechanical ventilation.
Adult Dose	MDI: 2-4 puffs q4h prn
Pediatric Dose	MDI: >20 kg: 6 puffs q20min initially Nebulizer: 0.15 mg/kg/dose in 2 mL in 0.9% NaCl administered q20min; not to exceed 5 mg/dose; alternatively, 0.5 mg/kg/h continuous nebulization; not to exceed 15 mg/h Oral: <2 years: Not established 2-6 years: 0.1 mg/kg PO up to 2 mg tid
Contraindications	Documented hypersensitivity
Interactions	Beta-adrenergic blockers antagonize effects; inhaled ipratropium may increase duration of bronchodilatation by albuterol; cardiovascular effects may increase with MAOIs, inhaled anesthetics, TCAs, and sympathomimetic agents
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in hyperthyroidism, diabetes mellitus, hypokalemia, muscle tremors, and cardiovascular disorders

Drug Name	Levalbuterol (Xopenex) -- Used for treatment or prevention of bronchospasm. A selective beta2-agonist agent. Albuterol is a racemic mixture, while levalbuterol contains only the active R-enantiomer of albuterol. The S-enantiomer does not bind to beta2-receptors but may be responsible for some adverse effects of racemic albuterol, including bronchial hyperreactivity and reduced pulmonary function during prolonged use.
Adult Dose	0.63 mg via nebulizer tid/qid; if response not adequate, may increase dose to 1.25 mg tid (but incidence of adverse effects may increase)
Pediatric Dose	<6 years: Not established 6-11 years: 0.31 mg via nebulizer tid, separate each dose by 6-8 h; not to exceed 0.63 mg tid >11 years: Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	Decreased efficacy with beta-blockers; digoxin levels may be decreased; may potentiate the kaliuretic effects of drugs such as loop or thiazide diuretics
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Doses higher than 0.63 mg tid may cause tachycardia; immediate hypersensitivity reactions reported; caution in patients with hypokalemia; may cause paradoxical bronchospasm and increased pulse rate or blood pressure

Drug Name	Terbutaline (Brethine) -- Acts directly on beta2-receptors to relax bronchial smooth muscle, relieving bronchospasm and reducing airway resistance.
Adult Dose	0.25 mg/dose SC repeated q20min once; not to exceed total dose of 0.5 mg in a 4-h period
Pediatric Dose	0.01 mg/kg SC up to 0.3 mg q20min up to 3 doses; alternatively, 2-10 mcg/kg IV loading dose over 10 min, then continuous IV infusion of 0.08-0.4 mcg/kg/min
Contraindications	Documented hypersensitivity; tachycardia resulting from cardiac arrhythmias
Interactions	Concomitant use with beta-blockers may inhibit bronchodilating, cardiac, and vasodilating effects of beta-agonists; concomitant administration of MAOIs may result in hypertensive crisis; concurrent administration of oxytocic drugs such as ergonovine with terbutaline may result in severe hypotension
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Paradoxical bronchoconstriction may occur with excessive use; through intracellular shunting, terbutaline may decrease serum potassium levels, which can produce adverse cardiovascular effects; decrease is usually transient and may not require supplementation

Drug Category: Anticholinergic agents -- These agents decrease muscle tone in the small and large pulmonary airways.

Drug Name	Ipratropium (Atrovent) -- A quaternary ammonium anticholinergic bronchodilator acting at muscarinic receptors of the parasympathetic nervous system. Chemically related to atropine. Has antisecretory properties and, when applied locally, inhibits secretions from serous and seromucous glands lining the nasal mucosa. Synergistic with beta2-agonists.
Adult Dose	MDI: 2-3 puffs qid
Pediatric Dose	Nebulizer: 500 mcg q20min for 3 doses, then q2-4h prn MDI: Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	Drugs with anticholinergic properties, such as dronabinol, may increase toxicity; albuterol increases effects of ipratropium
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Not indicated for acute episodes of bronchospasm; caution in narrow-angle glaucoma, prostatic hypertrophy, and bladder neck obstruction

Drug Category: Sympathomimetic agents -- These agents act to decrease the muscle tone in the small and large pulmonary airways.

Drug Name	Epinephrine (Adrenaline) -- Has alpha-agonist effects that include increased peripheral vascular resistance, reversed peripheral vasodilatation, systemic hypotension, and vascular permeability. Beta2-agonist effects include bronchodilatation, chronotropic cardiac activity, and positive inotropic effects.
Adult Dose	1:1000 solution (1 mg/mL) 0.1-0.5 mg SC q20min for 3 doses
Pediatric Dose	1:1000 solution (1 mg/mL) 0.01 mg/kg up to 0.3 mg/dose SC q20min for 3 doses <30 kg: EpiPen Jr (1:2000) SC delivers 0.15 mg/dose >30 kg: EpiPen (1:1000) SC delivers 0.3 mg/dose
Contraindications	Documented hypersensitivity; cardiac arrhythmias or angle-closure glaucoma; local anesthesia in areas such as fingers or toes because vasoconstriction may produce sloughing of tissue; not to use during labor (may delay second stage of labor)
Interactions	Increases toxicity of beta- and alpha-blocking agents and of halogenated inhalational anesthetics
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in elderly patients, prostatic hypertrophy, hypertension, cardiovascular disease, diabetes mellitus, hyperthyroidism, and cerebrovascular insufficiency; rapid IV infusions may cause death from cerebrovascular hemorrhage or cardiac arrhythmias

Drug Category: Methylxanthines -- These agents provide bronchodilation at the cellular level. The exact mechanism is unknown (eg, alteration of intracellular calcium, inhibition of phosphodiesterase, and/or antagonism of prostaglandins). Routine addition to beta-agonist provides benefit in ED management. May be of benefit in impending respiratory failure.

Drug Name	Theophylline, 85% (Aminophylline) -- Potentiates exogenous catecholamines, stimulates endogenous catecholamine release and diaphragmatic muscular relaxation, which, in turn, stimulates bronchodilation. For bronchodilation, near toxic (>20 mg/dL) levels are usually required. No role in acute asthma exacerbation. Considered in children who are responding poorly on maximal therapy.
Adult Dose	Loading dose: 6 mg/kg IV Maintenance dose: 0.7 mg/kg/h IV infusion
Pediatric Dose	Loading dose: 6 mg/kg IV infused over 20-30 min Maintenance dose: 6 weeks to 6 months: 0.5 mg/kg/h IV infusion 6 months to 1 year: 0.6-0.7 mg/kg/h IV infusion 1-9 years: 1-1.2 mg/kg/h IV infusion 9-12 years: 0.9 mg/kg/h IV infusion >12 years: Administer as in adults
Contraindications	Documented hypersensitivity; uncontrolled arrhythmias; peptic ulcers; hyperthyroidism; uncontrolled seizure disorders
Interactions	Aminoglutethimide, barbiturates, carbamazepine, ketoconazole, loop diuretics, charcoal, hydantoins, phenobarbital, phenytoin, rifampin, isoniazid, and sympathomimetics may decrease effects of theophylline; theophylline effects may increase with allopurinol, beta-blockers, ciprofloxacin, corticosteroids, disulfiram, quinolones, thyroid hormones, ephedrine, carbamazepine, cimetidine, erythromycin, macrolides, propranolol, and interferon
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in peptic ulcer, hypertension, tachyarrhythmias, hyperthyroidism, and compromised cardiac function; do not inject IV solution >25 mg/min; patients with pulmonary edema or liver dysfunction are at greater risk of toxicity because of reduced drug clearance

Drug Category: Magnesium salt -- These agents decrease acetylcholine release at the neuromuscular junction and may decrease resting tone of smooth muscle.

Drug Name	Magnesium sulfate -- Thought to produce bronchodilation through counteraction of calcium-mediated smooth muscle constriction.
Adult Dose	2 g IV over infused 30 min
Pediatric Dose	25 mg/kg IV not to exceed 2 g/dose
Contraindications	Documented hypersensitivity; heart block; Addison disease; myocardial damage; severe hepatitis
Interactions	Concurrent use with nifedipine may cause hypotension and neuromuscular blockade; may increase neuromuscular blockade observed with aminoglycosides and potentiate neuromuscular blockade produced by tubocurarine, vecuronium, and succinylcholine; may increase CNS effects and toxicity of CNS depressants, betamethasone, and cardiotoxicity of ritodrine
Pregnancy	A - Safe in pregnancy
Precautions	Magnesium may alter cardiac conduction leading to heart block in digitalized patients; respiratory rate, deep tendon reflex, and renal function should be monitored when electrolyte is administered parenterally; caution when administering magnesium dose because it may produce significant hypertension or asystole; in overdose, calcium gluconate, 10-20 mL IV of 10% solution, can be given as antidote for clinically significant hypermagnesemia

Drug Category: Gas mixture -- This agent is a blend of oxygen and helium that is less dense than air.

Drug Name	Helium and oxygen (Heliox) -- Reduces airway resistance in bronchi with turbulent flow because of low density. Decreases the work of breathing, hence, delaying the onset of respiratory muscle fatigue, allowing other therapies to work. Available in mixtures of 80:20 (helium:oxygen), 70:30, and 60:40.
Adult Dose	80:20 mixture at 10 L/min by nonrebreather mask; may increase to 15 L/min
Pediatric Dose	80:20 mixture at 10 L/min by nonrebreather mask
Contraindications	None reported
Interactions	None reported
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	None reported

Drug Category: General anesthetic -- Nonbarbiturate anesthetic/analgesic agent. An induction agent for airway management in patients with status asthmaticus and has a brief bronchodilatory effect.

Drug Name	Ketamine (Ketalar) -- Acts on the cortex and limbic system, decreasing bronchospasm.
Adult Dose	Intubation: 0.1 mg/kg IV followed by 0.5 mg/kg/h IV infusion for 3 h
Pediatric Dose	Intubation: 0.1 mg/kg IV followed by 0.5 mg/kg/h IV infusion for 3 h
Contraindications	Documented hypersensitivity; angina; thyrotoxicosis; aneurysms; hypertension; congestive heart failure
Interactions	Increases CNS effects of narcotics, barbiturates, and hydroxyzine; thyroid hormones and muscle relaxants increase toxicity of ketamine
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Resuscitative equipment should be immediately available during administration of medication

Drug Category: Mast cell stabilizers -- These agents inhibit degranulation of sensitized mast cells following exposure to specific antigens.

Drug Name	Cromolyn (Intal) -- Inhibits histamine release and slow-reacting substance of anaphylaxis from mast cell. MDI delivers 800 mcg/puff.
Adult Dose	MDI: 2-4 puffs qid
Pediatric Dose	MDI: 2 puffs tid/qid Nebulizer: 20 mg (2 mL) nebulized bid/qid
Contraindications	Documented hypersensitivity
Interactions	None reported
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Caution in severe renal or hepatic impairment; symptoms may reoccur when withdrawing drug

Drug Category: Leukotriene inhibitors -- These agents inhibit the synthesis of leukotriene.

Drug Name	Zileuton (Zyflo) -- Effective in aspirin-induced, cold air, and exercise-induced asthma. Not for use in acute episodes of asthma. Prophylactic use only. Hepatic transaminase levels should be evaluated before initiation. Contraindicated in patients with active liver disease.
Adult Dose	600 mg PO qid
Pediatric Dose	<12 years: Not recommended >12 years: Administer as in adults
Contraindications	Documented hypersensitivity; active liver disease
Interactions	Theophylline should be reduced by 50% for those taking both agents; coadministration with propranolol results in increased beta-blocker activity; coadministration with warfarin results in increased PT (monitor closely)
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in hepatic impairment, may increase LFTs

Drug Name	Zafirlukast (Accolate) -- Cysteinyl leukotriene-receptor antagonist. Inhibits aspirin-induced, cold air, and exercise-induced asthma. Not for use in acute episodes of asthma.
Adult Dose	20 mg PO bid between meals
Pediatric Dose	<5 years: Not established 5-11 years: 10 mg PO bid >12 years: Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	Erythromycin and theophylline reduce plasma concentrations; coadministration with warfarin results in increase in PT (monitor closely); coadministration with aspirin increases zafirlukast effects
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Not a bronchodilator; have appropriate rescue medication available; caution in hepatic impairment

Drug Name	Montelukast (Singulair) -- Cysteinyl leukotriene-receptor antagonist. Inhibits aspirin-induced, cold air, and exercise-induced asthma. Not for use in acute episodes of asthma.
Adult Dose	10 mg PO every evening
Pediatric Dose	<1 year: Not established 12-23 months: 1 packet of 4 mg oral granules PO every evening 2-5 years: 4 mg-chew tab or granules every evening 6-14 years: 5 mg PO every evening >14 years: Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	None reported
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Not a bronchodilator; have appropriate rescue medication available

Drug Category: Corticosteroids -- These agents have anti-inflammatory properties and cause profound and varied metabolic effects. They modify the body’s immune response to diverse stimuli. Oral prednisone should never be substituted for an inhaled corticosteroid in children with a severe acute asthma exacerbation.

Frequent use of inhaled corticosteroid therapy is associated with less ED visits and less hospitalizations. Current research has not proven any long-term adverse effects with children receiving long-term inhaled corticosteroid.

Drug Name	Methylprednisolone (Medrol, Solu-Medrol) -- For treatment of inflammatory and allergic reactions. By reversing increased capillary permeability and suppressing PMN activity, may decrease inflammation. Allows reduction of ongoing airway inflammation. May increase responsiveness to beta2-agonists by increasing the number of beta2-adrenergic receptors. Prophylactic inhaled steroids in those diagnosed with asthma may impede airway remodeling, bronchial hyperreactivity, and future airway damage. Systemic adverse effects rarely occur with inhaled corticosteroids. Systemic response time is the same in IV and PO. Steroid use is recommended if minimal improvement occurs after first beta2-agonist treatment, the patient was recently discontinued from steroids, the patient reports a history of asthma symptoms for a few days before presentation, or URI-associated symptoms are present.
Adult Dose	125 mg IV qid
Pediatric Dose	1-2 mg/kg/d PO qd or divided bid; 0.5-2 mg/kg/dose IV q6h Nebulization: Budesonide inhalation susp (Pulmicort) 2 mL plastic ampules containing 0.5 mg administer qd/bid in divided doses/primary use in those aged 12 mo to 8 y
Contraindications	Documented hypersensitivity; viral, fungal, or tubercular skin infections
Interactions	Coadministration with digoxin may increase digitalis toxicity secondary to hypokalemia; estrogens may increase levels of methylprednisolone; phenobarbital, phenytoin, and rifampin may decrease levels of methylprednisolone (adjust dose); monitor patients for hypokalemia when taking medication concurrently with diuretics
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Hyperglycemia, edema, osteonecrosis, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, growth suppression, myopathy, and infections are possible complications of glucocorticoid use

Drug Category: H2 receptor antagonists -- The combination of H1 and H2 antagonists may be useful in anaphylaxis not responding to H1 antagonists alone.

Drug Name	Cimetidine (Tagamet) -- If no response to H1 antagonist alone, coadministration with this H2 antagonist treats itching and flushing in anaphylaxis, pruritus, urticaria, and contact dermatitis.
Adult Dose	300-800 mg PO q6-8h; not to exceed 2400 mg/d 300 mg q6-8h IV/IM; not to exceed 2400 mg/d
Pediatric Dose	20-40 mg/kg/d (300 mg/5 mL syr) PO divided bid/qid
Contraindications	Documented hypersensitivity
Interactions	Can increase blood levels of theophylline, warfarin, tricyclic antidepressants, triamterene, phenytoin, quinidine, propranolol, metronidazole, procainamide, and lidocaine
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Elderly persons may experience confusional states; may cause impotence and gynecomastia in young males; may increase levels of many drugs; adjust dose or discontinue treatment if changes in renal function occur

FOLLOW-UP

Section 8 of 12

Further Inpatient Care:

• Consider admission if the initial peak expiratory flow rate (PEFR) is less than 20-25% of predicted and posttreatment is less than 70% of predicted or if no improvement occurs after 4 hours.

• If a child fails to improve within the first 2-3 hours of ED management, admission to an ED observation area, inpatient unit, or pediatric critical care unit is warranted.

• If the patient is able to ambulate and tolerate fluids in the ED without distress, discharge may be considered.

• Arrange for follow-up with the primary care physician or a pediatrician within 24 hours.

Further Outpatient Care:

• A follow-up visit with a primary care physician or pediatrician within 24 hours of the ED or inpatient visit is imperative.

• Air cleaners in homes in which there are pets may be helpful for young patients with asthma.

Deterrence/Prevention:

• Parents of asthmatic children should have at least 2 sets of inhalers (eg, one for school and one for home).

• After an asthma exacerbation, the child may return to school when asymptomatic and the PEFR is within 20% of normal.

• Reduction in allergen exposure results in reduction of asthma and rhinitis symptoms and medications needed.

• Avoid outdoor exposure and/or physical activity during periods of high smog alerts in community.

• Change home furnace filters, remove dust, change linen, and vacuum regularly to reduce potential triggers.

• Avoid second-hand tobacco smoke, a well-known trigger of asthma attacks in infants and children.

Complications:

• Respiratory failure/mechanical ventilation

• Atelectasis

• Flaccid paralysis (self-limited)

• Death

• Pneumothorax

• Syndrome of inappropriate antidiuretic hormone secretion (SIADH)

• Altered theophylline metabolism

Prognosis:

• The prognosis is excellent with attention to general health and appropriate use of medications.

• Fewer than 50% of patients "out grow" asthma.

• Increased mortality risk

• More than 3 ED visits per year

• Nocturnal symptoms

• History of ICU admission

• Mechanical ventilation

• More than 2 hospitalizations per year

• Steroid dependence

• History of syncope

Patient Education:

• Monitoring PEFR is an easily performed test that can be mastered for those as young as 3-4 years. PEFR monitoring is an important tool in asthma management that uses a zone system to optimize effectiveness of asthma control.

• Green zone (80-100% predicted or child's best) - Good control

• Yellow zone (50-80%) - Necessitates increased awareness and treatment

• Red zone ( <50%) - Poor control, requires immediate intervention

• Educate children and their families about asthma.

• Avoidance of potential triggers.

• Emphasis on the use of anti-inflammatory inhalation

• Instruct on peak expiratory flow and symptom monitoring

• Spacer devices should be used in all children with asthma. They improve the deposition of drug into the lower airway, hence improving efficacy of medication.

• For excellent patient education resources, see eMedicine's Asthma Center. Also, visit eMedicine's patient education article, Asthma.

MISCELLANEOUS

Section 9 of 12

Medical/Legal Pitfalls:

• Failure to initiate steroid therapy

• Discharging a patient with abnormal vital signs without an explanation

• Discharging a patient with a high respiratory rate or with oxygen saturation less than 94%

• Early intubation

• Barotrauma after intubation due to inappropriate volumes

Special Concerns:

• Gastroesophageal reflux (GER) is common in asthmatic children. Proton-pump inhibitor therapy may help. In those with abnormal esophageal pH monitoring, severe persistent asthma and recurrent pneumonia, surgical therapy for GER may be an option. Infants may improve with alterations in feeding strategy.

TEST QUESTIONS

Section 10 of 12

CME Question 1: Which of the following is not an indication for admission for asthma?

A: Near-fatal experience with previous asthma exacerbation
B: Peak expiratory flow rate of less than 60% of predicted after aggressive ED therapy
C: Arterial oxygen saturation (SaO₂) of 91% or less after aggressive ED therapy
D: PCO₂ greater than 35 mm Hg
E: Pulsus paradoxus of 10 mm Hg

The correct answer is E: Mild asthma is defined as pulsus paradoxus of less than 10 mm Hg; moderate, 10-20 mm Hg; and severe, greater than 20 mm Hg.

CME Question 2: What are the most common precipitants of reactive airway disease in children younger than 2 years?

A: Dust mites
B: Viral infections
C: Gastroesophageal reflux
D: Cigarette smoke
E: None of the above

The correct answer is B: Reactive airway disease is most commonly caused by respiratory syncytial virus, rhinovirus, parainfluenza virus, and influenza virus.

Pearl Question 1 (T/F): Nebulized delivery of beta-agonists is superior to metered-dose inhaler (MDI) with spacer.

The correct answer is False: MDI-spacer and nebulizer have equivalent efficacy. Convincing patients to use the MDI-spacer may be difficult since most patients were using the MDI-spacer prior to arrival without improvement. Education on the correct use of the MDI-spacer in the emergency department may result in cost savings.

Pearl Question 2 (T/F): Admission rates are reduced with early corticosteroid therapy in severe asthmatics.

The correct answer is True: Intravenous administration shows no advantage over oral administration of corticosteroids. A low dose of corticosteroid is effective. Inhaled corticosteroid treatment appears to be promising, but further study is needed.

Pearl Question 3 (T/F): Ipratropium bromide has shown clear benefit in children with asthma.

The correct answer is True: Multiple-dose therapy significantly reduces admissions and appears to improve pulmonary functions.

Pearl Question 4 (T/F): A chest radiograph should be taken on every child younger than 1 year and with a first episode of wheezing or chronic cough.

The correct answer is True: A chest radiograph should be taken to rule out foreign body, heart disease, parenchymal lung disease, and congenital abnormalities.

PICTURES

Section 11 of 12

Caption: Picture 1. Patient peak flow record.
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Caption: Picture 2. This nomogram results from tests carried out by S. Godfrey, MD, and his colleagues on a sample of 382 healthy boys and girls aged 5-18 years. Each child blew 5 times into a standard Wright Peak Flow Meter, and the highest reading was accepted in each in each case. All measurements were completed within a 6-week period. The outer lines of the graph indicated that the results of 95% of the children fell within these boundaries.
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BIBLIOGRAPHY

Section 12 of 12

• Amirav I, Newhouse MT: Metered-dose inhaler accessory devices in acute asthma: efficacy and comparison with nebulizers: a literature review. Arch Pediatr Adolesc Med 1997 Sep; 151(9): 876-82[Medline].
• Apter AJ, Szefler SJ: Advances in adult and pediatric asthma. J Allergy Clin Immunol 2004 Mar; 113(3): 407-14[Medline].
• Baren JM, Zorc JJ: Contemporary approach to the emergency department management of pediatric asthma. Emerg Med Clin North Am 2002 Feb; 20(1): 115-38[Medline].
• Beasley R, Crane J, Lai CK, Pearce N: Prevalence and etiology of asthma. J Allergy Clin Immunol 2000 Feb; 105(2 Pt 2): S466-72[Medline].
• Becker A, Watson W, Ferguson A, et al: The Canadian asthma primary prevention study: outcomes at 2 years of age. J Allergy Clin Immunol 2004 Apr; 113(4): 650-6[Medline].
• Clainche LL, Timsit S, Rigourd V, et al: Asthma and the child below 5 years of age: diagnosis and treatment [in French]. Rev Mal Respir 2000 Feb; 17(1 Pt 2): 213-23[Medline].
• Craig VL, Bigos D, Brilli RJ: Efficacy and safety of continuous albuterol nebulization in children with severe status asthmaticus. Pediatr Emerg Care 1996 Feb; 12(1): 1-5[Medline].
• Crain EF, Mortimer KM, Bauman LJ, et al: Pediatric asthma care in the emergency department: measuring the quality of history-taking and discharge planning. J Asthma 1999; 36(1): 129-38[Medline].
• Csonka P, Mertsola J, Klaukka T, et al: Corticosteroid therapy and need for hospital care in wheezing preschool children. Eur J Clin Pharmacol 2000 Nov; 56(8): 591-6[Medline].
• Darr CD: Asthma and bronchiolitis. In: Emergency Medicine: Concepts and Clinical Practice. 4th ed. 1998:1137-45.
• Eggleston PA, Wood RA, Rand C, et al: Removal of cockroach allergen from inner-city homes. J Allergy Clin Immunol 1999 Oct; 104(4 Pt 1): 842-6[Medline].
• Farber HJ, Johnson C, Beckerman RC: Young inner-city children visiting the emergency room (ER) for asthma: risk factors and chronic care behaviors. J Asthma 1998; 35(7): 547-52[Medline].
• Garde Garde Jf, Haro E, Sanchez-Lucas C, Garde Noguera J: Antileukotrienes. Their use in pediatrics [in Spanish]. Allergol Immunopathol (Madr) 2000 May-Jun; 28(3): 136-43[Medline].
• Gibbs MA, Camargo CA, Rowe BH, Silverman RA: State of the art: therapeutic controversies in severe acute asthma. Acad Emerg Med 2000 Jul; 7(7): 800-15[Medline].
• Hsu KH, Jenkins DE, Hsi BP, et al: Ventilatory functions of normal children and young adults--Mexican- American, white, and black. II. Wright peak flowmeter. J Pediatr 1979 Aug; 95(2): 192-6[Medline].
• Kellner JD, Ohlsson A, Gadomski AM, Wang EE: Efficacy of bronchodilator therapy in bronchiolitis. A meta-analysis. Arch Pediatr Adolesc Med 1996 Nov; 150(11): 1166-72[Medline].
• Kemp JP, Dockhorn RJ, Shapiro GG, et al: Montelukast once daily inhibits exercise-induced bronchoconstriction in 6- to 14-year-old children with asthma. J Pediatr 1998 Sep; 133(3): 424-8[Medline].
• Kitch BT, Chew G, Burge HA, et al: Socioeconomic predictors of high allergen levels in homes in the greater Boston area. Environ Health Perspect 2000 Apr; 108(4): 301-7[Medline].
• Le Clainche L, Timsit S, Rigourd V, et al: Asthma in children below 5 years of age: diagnosis and treatment. Rev Mal Respir 1999 Feb; 16(1): 17-27[Medline].
• Litonjua AA, Carey VJ, Burge HA, et al: Exposure to cockroach allergen in the home is associated with incident doctor-diagnosed asthma and recurrent wheezing. J Allergy Clin Immunol 2001 Jan; 107(1): 41-7[Medline].
• Newson T, McKenzie S: Cough and asthma in children. Pediatr Ann 1996 Mar; 25(3): 156-8, 161[Medline].
• Qureshi F, Zaritsky A, Lakkis H: Efficacy of nebulized ipratropium in severely asthmatic children. Ann Emerg Med 1997 Feb; 29(2): 205-11[Medline].
• Roback MG, Dreitlein DA: Chest radiograph in the evaluation of first time wheezing episodes: review of current clinical practice and efficacy. Pediatr Emerg Care 1998 Jun; 14(3): 181-4[Medline].
• Rosenstreich DL, Eggleston P, Kattan M, et al: The role of cockroach allergy and exposure to cockroach allergen in causing morbidity among inner-city children with asthma. N Engl J Med 1997 May 8; 336(19): 1356-63[Medline].
• Rubin BK, Albers GM: Use of anticholinergic bronchodilation in children. Am J Med 1996 Jan 29; 100(1A): 49S-53S[Medline].
• Rudolph CD: Supraesophageal complications of gastroesophageal reflux in children: challenges in diagnosis and treatment. Am J Med 2003 Aug 18; 115 Suppl 3A: 150S-156S[Medline].
• Schreck DM, Babin S: Comparison of racemic albuterol and levalbuterol in the treatment of acute asthma in the ED. Am J Emerg Med 2005 Nov; 23(7): 842-7[Medline].
• Schuh S, Reisman J, Alshehri M, et al: A comparison of inhaled fluticasone and oral prednisone for children with severe acute asthma. N Engl J Med 2000 Sep 7; 343(10): 689-94[Medline].
• Spahn JD: Pharmacologic management of pediatric asthma. 1998; 18 (1): 165-81.
• Stempel DA, Meyer JW, Stanford RH, Yancey SW.: One-year claims analysis comparing inhaled fluticasone propionate with zafirlukast for the treatment of asthma. J Allergy Clin Immunol 2001 Jan; 107(1): 94-8[Medline].
• Steyer TE, Mallin R, Blair M: Pediatric asthma. Clinics in Family Practice 2003 Jun; 5.
• Suissa S, Ernst P, Benayoun S, et al: Low-dose inhaled corticosteroids and the prevention of death from asthma. N Engl J Med 2000 Aug 3; 343(5): 332-6[Medline].
• Sun HL, Chou MC, Lue KH, et al: The relationship of air pollution to ED visits for asthma differ between children and adults. Am J Emerg Med 2006 Oct; 24(6): 709-13[Medline].
• Walsh-Kelly CM, Kim MK, Hennes HM: Chest radiography in the initial episode of bronchospasm in children: can clinical variables predict pathologic findings? Ann Emerg Med 1996 Oct; 28(4): 391-5[Medline].
• Welliver RC: Immunologic mechanisms of virus-induced wheezing and asthma. J Pediatr 1999 Aug; 135(2 Pt 2): 14-20[Medline].
• Werk LN, Steinbach S, Adams WG, Bauchner H: Beliefs about diagnosing asthma in young children. Pediatrics 2000 Mar; 105(3 Pt 1): 585-90[Medline].
• Williams JR, Bothner JP, Swanton RD: Delivery of albuterol in a pediatric emergency department. Pediatr Emerg Care 1996 Aug; 12(4): 263-7[Medline].
• Wolfram RW: Asthma. In: The Clinical Practice of Emergency Medicine. 2nd ed. 1997:1093-96.
• Zeffren BS, Windom HH, Bahna SL: Modern treatment of asthma in children. In: Mosby Year Book. 43: 1996:423-68.

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